title: Length polymorphism in heme oxygenase-1 and cardiovascular events and mortality in hemodialysis patients.
abstract: OBJECTIVE
  Persistent inflammation and oxidative stress play a pathogenic role in the high cardiovascular morbidity and mortality of hemodialysis patients. Heme oxygenase-1 is considered to have anti-inflammatory and antioxidant properties. This study assessed the association between the length of guanosine thymidine dinucleotide repeats in the heme oxygenase-1 gene microsatellite promoter and cardiovascular events and mortality among hemodialysis patients.
  
  
  METHODS
  Study participants were recruited from October 1, 2006 to December 31, 2006. The allelic frequencies of the length of guanosine thymidine dinucleotide repeats (the S allele represents shorter [<27] repeats, and the L allele represents longer [≥ 27] repeats) in the heme oxygenase-1 gene promoter were analyzed in 1080 unrelated chronic hemodialysis patients and 365 healthy controls for distribution comparison. Cardiovascular events and mortality were the study outcomes, and the hemodialysis patients were followed until June 30, 2011.
  
  
  RESULTS
  The genotype proportions were 20.6%, 48.8%, and 30.6% for S/S, S/L, and L/L, respectively, in the hemodialysis patients and comparable with those proportions in healthy controls. The patients with the L/L genotype had significantly higher baseline serum high-sensitivity C-reactive protein and malondialdehyde levels than the patients with the S/S or S/L genotypes. During a median follow-up of 50 months, 307 patients died. A Kaplan-Meier survival analysis showed the highest cardiovascular events and all-cause mortality in patients with the L/L genotype. The adjusted hazard ratios (95% confidence intervals) for each L allele in additive model were 1.42 (1.20 to 1.67 [P<0.001]) for cardiovascular events and 1.19 (1.01 to 1.40 [P=0.03]) for all-cause mortality.
  
  
  CONCLUSIONS
  Chronic hemodialysis patients with longer lengths of guanosine thymidine dinucleotide repeats in the heme oxygenase-1 gene promoter exhibit higher inflammation and oxidative stress. These patients have higher risk of long-term cardiovascular events and mortality.
authors.affiliation: Department of Medicine, Taipei Veterans General Hospital, Su-Ao Branch, Yilan, Taiwan;, †Faculty of Medicine and, ‖Department and Institute of Physiology, National Yang-Ming University, Taipei, Taiwan;, ‡Division of Nephrology, Buddhist Tzu Chi General Hospital, Taipei Branch, Taipei, Taiwan, §Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Yu-Hsin
authors.initials: YH
authors.lastname: Chen
authors.forename: Szu-Chun
authors.initials: SC
authors.lastname: Hung
authors.forename: Der-Cherng
authors.initials: DC
authors.lastname: Tarng
mesh_terms: D000328:Adult; D000368:Aged; D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000209:etiology*; D005260:Female; D005838:Genotype; D051547:Heme Oxygenase-1 / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000401:mortality
chemical_list: D002097:C-Reactive Protein; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1